ABSTRACT
Indigenous communities in the North American Arctic are characterized by mixed economies that feature hunting, fishing, gathering, and trapping activities-and associated sharing practices-alongside the formal wage economy. The region is also undergoing rapid social, economic, and climate changes, including, in Canada, carbon taxation, which is impacting the cost of fuel used in local food harvesting. Because of the importance of local foods to nutrition, health, and well-being in Arctic Indigenous communities, there is an urgent need to better understand the sensitivity of Arctic food systems to social, economic, and climate changes and to develop plans for mitigating potential adverse effects. Here, we develop a Bayesian model to calculate the substitution value and carbon emissions of market replacements for local food harvests in the Inuvialuit Settlement Region, Canada. Our estimates suggest that under plausible scenarios, replacing locally harvested foods with imported market substitutes would cost over 3.1 million Canadian dollars per year and emit over 1,000 tons of CO2-equivalent emissions per year, regardless of the shipping scenario. In contrast, we estimate that gasoline inputs to harvesting cost approximately $295,000 and result in 315 to 497 tons of emissions. These results indicate that climate change policies that fail to account for local food production may undermine emissions targets and adversely impact food security and health in Arctic Indigenous communities, who already experience a high cost of living and high rates of food insecurity.
Subject(s)
Climate Change , Food Supply , Canada , Food Supply/economics , Humans , Climate Change/economics , Arctic Regions , Bayes Theorem , Carbon/metabolism , Indigenous Peoples , Food/economics , Carbon Dioxide/analysis , Carbon Dioxide/metabolismABSTRACT
Humans cooperate in groups in which mutual monitoring is common, and this provides the possibility of third-party arbitration. Third-party arbitration stabilizes reciprocity in at least two ways: first, when it is accurate, it reduces the frequency of misunderstandings resulting from perception errors, and second, even when it is inaccurate, it provides a public signal that allows pairs to align their expectations about how to behave after errors occur. Here, we describe experiments that test for these two effects. We find that in an iterated, sequential Prisoner's Dilemma game with errors, players with the highest average payoffs are those who make use of third-party arbitration and who also employ forgiving strategies. The combination of these two behaviours reduces the detrimental effects of errors on reciprocity, resulting in more cooperation.
Subject(s)
Cooperative Behavior , Humans , Prisoner Dilemma , Negotiating , Perception , Game Theory , Forgiveness , Interpersonal RelationsABSTRACT
Cis-regulatory elements (CREs) interact with trans regulators to orchestrate gene expression, but how transcriptional regulation is coordinated in multi-gene loci has not been experimentally defined. We sought to characterize the CREs controlling dynamic expression of the adjacent costimulatory genes CD28, CTLA4 and ICOS, encoding regulators of T cell-mediated immunity. Tiling CRISPR interference (CRISPRi) screens in primary human T cells, both conventional and regulatory subsets, uncovered gene-, cell subset- and stimulation-specific CREs. Integration with CRISPR knockout screens and assay for transposase-accessible chromatin with sequencing (ATAC-seq) profiling identified trans regulators influencing chromatin states at specific CRISPRi-responsive elements to control costimulatory gene expression. We then discovered a critical CCCTC-binding factor (CTCF) boundary that reinforces CRE interaction with CTLA4 while also preventing promiscuous activation of CD28. By systematically mapping CREs and associated trans regulators directly in primary human T cell subsets, this work overcomes longstanding experimental limitations to decode context-dependent gene regulatory programs in a complex, multi-gene locus critical to immune homeostasis.
Subject(s)
CD28 Antigens , CTLA-4 Antigen , Chromatin , Gene Expression Regulation , Humans , CTLA-4 Antigen/genetics , CD28 Antigens/genetics , Chromatin/genetics , Chromatin/metabolism , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Inducible T-Cell Co-Stimulator Protein/genetics , Inducible T-Cell Co-Stimulator Protein/metabolism , CCCTC-Binding Factor/metabolism , CCCTC-Binding Factor/genetics , CRISPR-Cas SystemsABSTRACT
Although still prevalent in many human societies, the practice of cousin marriage has precipitously declined in populations undergoing rapid demographic and socioeconomic change. However, it is still unclear whether changes in the structure of the marriage pool or changes in the fitness-relevant consequences of cousin marriage more strongly influence the frequency of cousin marriage. Here, we use genealogical data collected by the Tsimane Health and Life History Project to show that there is a small but measurable decline in the frequency of first cross-cousin marriage since the mid-twentieth century. Such changes are linked to concomitant changes in the pool of potential spouses in recent decades. We find only very modest differences in fitness-relevant demographic measures between first cousin and non-cousin marriages. These differences have been diminishing as the Tsimane have become more market integrated. The factors that influence preferences for cousin marriage appear to be less prevalent now than in the past, but cultural inertia might slow the pace of change in marriage norms. Overall, our findings suggest that cultural changes in marriage practices reflect underlying societal changes that shape the pool of potential spouses.
ABSTRACT
Copines are a family of calcium-dependent membrane-binding proteins. To study these proteins, anull mutant for cpnC was created in Dictyostelium, which has six copines genes (cpnA-cpnF). During development, cpnC- cells were able to aggregate, but did not form streams. Once aggregated into mounds, they formed large ring structures. cpnC- cells were less adherent to plastic substrates, but more adherent to other cells. These phenotypes correlated with changes in adhesion protein expression with decreased expression of SibA and increased expression of CsaA in developing cpnC- cells. We also measured the expression of RegA, a cAMP phosphodiesterase, and found that cpnC- cells have reduced RegA expression. The reduced RegA expression in cpnC- cells is most likely responsible for the observed phenotypes.
Subject(s)
Dictyostelium , Dictyostelium/genetics , Carrier Proteins/geneticsABSTRACT
While it is commonly assumed that farmers have higher, and foragers lower, fertility compared to populations practicing other forms of subsistence, robust supportive evidence is lacking. We tested whether subsistence activities-incorporating market integration-are associated with fertility in 10,250 women from 27 small-scale societies and found considerable variation in fertility. This variation did not align with group-level subsistence typologies. Societies labeled as "farmers" did not have higher fertility than others, while "foragers" did not have lower fertility. However, at the individual level, we found strong evidence that fertility was positively associated with farming and moderate evidence of a negative relationship between foraging and fertility. Markers of market integration were strongly negatively correlated with fertility. Despite strong cross-cultural evidence, these relationships were not consistent in all populations, highlighting the importance of the socioecological context, which likely influences the diverse mechanisms driving the relationship between fertility and subsistence.
Subject(s)
Economics , Fertility , Female , Humans , Population Dynamics , Socioeconomic Factors , Developing CountriesABSTRACT
In hunter-gatherer societies, women's subsistence activities are crucial for food provisioning and children's social learning but are understudied relative to men's activities. To understand the structure of women's foraging networks, we present 230 days of focal-follow data in a BaYaka community. To analyze these data, we develop a stochastic blockmodel for repeat observations with uneven sampling. We find that women's subsistence networks are characterized by cooperation between kin, gender homophily, and mixed age-group composition. During early childhood, individuals preferentially coforage with adult kin, but those in middle childhood and adolescence are likely to coforage with nonkin peers, providing opportunities for horizontal learning. By quantifying the probability of coforaging ties across age classes and relatedness levels, our findings provide insights into the scope for social learning during women's subsistence activities in a real-world foraging population and provide ground-truth values for key parameters used in formal models of cumulative culture.
Subject(s)
Food , Learning , Child , Child, Preschool , Adolescent , Adult , Male , Humans , Female , Congo , ProbabilityABSTRACT
There have been recent calls for wider application of generative modelling approaches in applied social network analysis. At present, however, it remains difficult for typical end users-for example, field researchers-to implement generative network models, as there is a dearth of openly available software packages that make application of such models as simple as other, permutation-based approaches. Here, we outline the STRAND R package, which provides a suite of generative models for Bayesian analysis of animal social network data that can be implemented using simple, base R syntax. To facilitate ease of use, we provide a tutorial demonstrating how STRAND can be used to model proportion, count or binary network data using stochastic block models, social relation models or a combination of the two modelling frameworks. STRAND facilitates the application of generative network models to a broad range of data found in the animal social networks literature.
Subject(s)
Software , Animals , Bayes TheoremABSTRACT
BACKGROUND: Patients undergoing hip arthroscopy performed with perineal post distraction may experience postoperative nerve and soft tissue complications related to the perineal post. PURPOSE: To compare rates of postoperative numbness in patients undergoing hip arthroscopy for femoroacetabular impingement syndrome (FAIS) with postless distraction and perineal post distraction methods. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A retrospective review of prospectively collected data was performed on patients who underwent hip arthroscopy for FAIS, with postless distraction and perineal post distraction methods. Medical records were reviewed for patient characteristics, radiographic data, and operative data. Traction force data were collected on all patients prospectively using a previously validated method. Data on postoperative numbness (presence/absence and regionality) were collected prospectively at routine postoperative follow-ups (6-week and 3-month postoperative clinic visits). RESULTS: Overall, 195 patients were included, with 94 patients (mean age, 30.4 years) in the postless distraction cohort and 101 patients (mean age, 31.9 years) in the post distraction cohort. The overall numbness rates were 29 of 94 (30.9%) in the postless distraction group and 45 of 101 (44.6%) in the post distraction group (P = .068). Rates of postoperative groin numbness were 1 of 94 (1.1%) in the postless distraction group and 19 of 101 (18.8%) in the post distraction group (P < .001). Multivariate analysis for postoperative groin numbness demonstrated post distraction (odds ratio [OR], 16.5; P = .022) and traction time (OR, 1.7; P = .020) to be statistically significant variables. In subgroup analysis of the post distraction group, traction time (P = .015), but not holding (P = .508) or maximum traction force (P = .665), reached statistical significance in patients who developed postoperative groin numbness. CONCLUSION: Postless distraction hip arthroscopy demonstrated a statistically significantly lower rate of groin numbness rates in comparison with a traditional perineal post distraction method. In the post distraction group, traction time was significantly higher in patients who developed postoperative groin numbness than in those who did not.
Subject(s)
Femoracetabular Impingement , Hip Joint , Humans , Adult , Hip Joint/surgery , Groin , Arthroscopy/adverse effects , Arthroscopy/methods , Cohort Studies , Hypesthesia/epidemiology , Hypesthesia/etiology , Femoracetabular Impingement/surgery , Retrospective Studies , Treatment Outcome , Activities of Daily Living , Follow-Up StudiesABSTRACT
Chronic stimulation can cause T cell dysfunction and limit the efficacy of cellular immunotherapies. Improved methods are required to compare large numbers of synthetic knockin (KI) sequences to reprogram cell functions. Here, we developed modular pooled KI screening (ModPoKI), an adaptable platform for modular construction of DNA KI libraries using barcoded multicistronic adaptors. We built two ModPoKI libraries of 100 transcription factors (TFs) and 129 natural and synthetic surface receptors (SRs). Over 30 ModPoKI screens across human TCR- and CAR-T cells in diverse conditions identified a transcription factor AP4 (TFAP4) construct that enhanced fitness of chronically stimulated CAR-T cells and anti-cancer function in vitro and in vivo. ModPoKI's modularity allowed us to generate an â¼10,000-member library of TF combinations. Non-viral KI of a combined BATF-TFAP4 polycistronic construct enhanced fitness. Overexpressed BATF and TFAP4 co-occupy and regulate key gene targets to reprogram T cell function. ModPoKI facilitates the discovery of complex gene constructs to program cellular functions.
Subject(s)
Cell- and Tissue-Based Therapy , Exercise , Humans , Gene Library , Immunotherapy , ResearchABSTRACT
Cousin marriage, a spousal union between close kin, occurs at high frequencies in many parts of the world. The rates of cousin marriage in humans are concordant with empirical studies that challenge the traditionally held view that reproduction with kin is generally avoided in animals. Similarly, some theoretical models in animal behaviour show that inbreeding avoidance is more constrained than previously thought. Such studies highlight the importance of quantifying the costs and benefits of reproduction among close kin over the whole life-course. Here, we use genealogical data from two human populations with high frequencies of cousin marriage (the Dogon from Mali, and the Ancien Régime nobility from Europe) to estimate these potential costs and benefits. We compare age-specific fertility and survival curves, as well as the projected growth rates, of subpopulations of each marriage type. Fitness costs of cousin marriage are present in terms of reduced child survival (in both populations), while benefits exist as increased fertility for men (in the Dogon) and for women (in the Ancien Régime nobility). We also find some differences in the projected growth rates of lineages as a function of marriage type. Finally, we discuss the trade-offs that might shape marriage decisions in different ecological conditions.
ABSTRACT
Intermolecular interactions on inorganic substrates can have a critical impact on the electrochemical and photophysical properties of the materials and subsequent performance in hybrid electronics. Critical to the intentional formation or inhibition of these processes is controlling interactions between molecules on a surface. In this report, we investigated the impact of surface loading and atomic-layer-deposited Al2O3 overlayers on the intermolecular interactions of a ZrO2-bound anthracene derivative as probed by the photophysical properties of the interface. While surface loading density had no impact on the absorption spectra of the films, there was an increase in excimer features with surface loading as observed by both emission and transient absorption. The addition of ALD overlayers of Al2O3 resulted in a decrease in excimer formation, but the emission and transient absorption spectra were still dominated by excimer features. These results suggest that ALD may provide a post-surface loading means of influencing such intermolecular interactions.
ABSTRACT
To address claims of human exceptionalism, we determine where humans fit within the greater mammalian distribution of reproductive inequality. We show that humans exhibit lower reproductive skew (i.e., inequality in the number of surviving offspring) among males and smaller sex differences in reproductive skew than most other mammals, while nevertheless falling within the mammalian range. Additionally, female reproductive skew is higher in polygynous human populations than in polygynous nonhumans mammals on average. This patterning of skew can be attributed in part to the prevalence of monogamy in humans compared to the predominance of polygyny in nonhuman mammals, to the limited degree of polygyny in the human societies that practice it, and to the importance of unequally held rival resources to women's fitness. The muted reproductive inequality observed in humans appears to be linked to several unusual characteristics of our species-including high levels of cooperation among males, high dependence on unequally held rival resources, complementarities between maternal and paternal investment, as well as social and legal institutions that enforce monogamous norms.
Subject(s)
Reproduction , Sex Characteristics , Animals , Humans , Female , Male , Marriage , Mammals , Sexual Behavior, AnimalABSTRACT
Social network analysis provides an important framework for studying the causes, consequences, and structure of social ties. However, standard self-report measures-for example, as collected through the popular "name-generator" method-do not provide an impartial representation of such ties, be they transfers, interactions, or social relationships. At best, they represent perceptions filtered through the cognitive biases of respondents. Individuals may, for example, report transfers that did not really occur, or forget to mention transfers that really did. The propensity to make such reporting inaccuracies is both an individual-level and item-level characteristic-variable across members of any given group. Past research has highlighted that many network-level properties are highly sensitive to such reporting inaccuracies. However, there remains a dearth of easily deployed statistical tools that account for such biases. To address this issue, we provide a latent network model that allows researchers to jointly estimate parameters measuring both reporting biases and a latent, underlying social network. Building upon past research, we conduct several simulation experiments in which network data are subject to various reporting biases, and find that these reporting biases strongly impact fundamental network properties. These impacts are not adequately remedied using the most frequently deployed approaches for network reconstruction in the social sciences (i.e., treating either the union or the intersection of double-sampled data as the true network), but are appropriately resolved through the use of our latent network models. To make implementation of our models easier for end-users, we provide a fully documented R package, STRAND, and include a tutorial illustrating its functionality when applied to empirical food/money sharing data from a rural Colombian population. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
ABSTRACT
Intergroup and long-distance relationships are both central features of human social life, but because intergroup relationships are emphasized in the literature, long-distance relationships are often overlooked. Here, we make the case that intergroup and long-distance relationships should be studied as distinct, albeit related, features of human sociality. First, we review the functions of both kinds of relationship: while both can be conduits for difficult-to-access resources, intergroup relationships can reduce intergroup conflict whereas long-distance relationships are especially effective at buffering widespread resource shortfalls. Second, to illustrate the importance of distinguishing the two relationship types, we present a case study from rural Bolivia. Combining ethnography and two different experimental techniques, we find that the importance of intergroup relationships-and the salience of group membership itself-varies across populations and across methods. Although ethnography revealed that participants often rely on long-distance relationships for resource access, we were unable to capture participant preferences for these relationships with a forced-choice technique. Taken together, our review and empirical data highlight that (1) intergroup and long-distance relationships can have different functions and can be more or less important in different contexts and (2) validating experimental field data with ethnography is crucial for work on human sociality. We close by outlining future directions for research on long-distance relationships in humans.
Subject(s)
Interpersonal Relations , Social Behavior , Humans , BoliviaABSTRACT
When interacting with infants, humans often alter their speech and song in ways thought to support communication. Theories of human child-rearing, informed by data on vocal signalling across species, predict that such alterations should appear globally. Here, we show acoustic differences between infant-directed and adult-directed vocalizations across cultures. We collected 1,615 recordings of infant- and adult-directed speech and song produced by 410 people in 21 urban, rural and small-scale societies. Infant-directedness was reliably classified from acoustic features only, with acoustic profiles of infant-directedness differing across language and music but in consistent fashions. We then studied listener sensitivity to these acoustic features. We played the recordings to 51,065 people from 187 countries, recruited via an English-language website, who guessed whether each vocalization was infant-directed. Their intuitions were more accurate than chance, predictable in part by common sets of acoustic features and robust to the effects of linguistic relatedness between vocalizer and listener. These findings inform hypotheses of the psychological functions and evolution of human communication.
Subject(s)
Music , Voice , Humans , Adult , Infant , Speech , Language , AcousticsABSTRACT
Archaea synthesize isoprenoid-based ether-linked membrane lipids, which enable them to withstand extreme environmental conditions, such as high temperatures, high salinity, and low or high pH values1-5. In some archaea, such as Methanocaldococcus jannaschii, these lipids are further modified by forming carbon-carbon bonds between the termini of two lipid tails within one glycerophospholipid to generate the macrocyclic archaeol or forming two carbon-carbon bonds between the termini of two lipid tails from two glycerophospholipids to generate the macrocycle glycerol dibiphytanyl glycerol tetraether (GDGT)1,2. GDGT contains two 40-carbon lipid chains (biphytanyl chains) that span both leaflets of the membrane, providing enhanced stability to extreme conditions. How these specialized lipids are formed has puzzled scientists for decades. The reaction necessitates the coupling of two completely inert sp3-hybridized carbon centres, which, to our knowledge, has not been observed in nature. Here we show that the gene product of mj0619 from M. jannaschii, which encodes a radical S-adenosylmethionine enzyme, is responsible for biphytanyl chain formation during synthesis of both the macrocyclic archaeol and GDGT membrane lipids6. Structures of the enzyme show the presence of four metallocofactors: three [Fe4S4] clusters and one mononuclear rubredoxin-like iron ion. In vitro mechanistic studies show that Csp3-Csp3 bond formation takes place on fully saturated archaeal lipid substrates and involves an intermediate bond between the substrate carbon and a sulfur of one of the [Fe4S4] clusters. Our results not only establish the biosynthetic route for tetraether formation but also improve the use of GDGT in GDGT-based paleoclimatology indices7-10.
Subject(s)
Archaeal Proteins , Glyceryl Ethers , Membrane Lipids , Methanocaldococcus , Archaeal Proteins/chemistry , Archaeal Proteins/isolation & purification , Archaeal Proteins/metabolism , Carbon/chemistry , Carbon/metabolism , Glycerol/chemistry , Glycerol/metabolism , Glyceryl Ethers/chemistry , Glyceryl Ethers/metabolism , Membrane Lipids/biosynthesis , Membrane Lipids/chemistry , Membrane Lipids/metabolism , Methanocaldococcus/chemistry , Methanocaldococcus/enzymology , Methanocaldococcus/metabolism , S-Adenosylmethionine/metabolism , Terpenes/chemistry , Terpenes/metabolismABSTRACT
We evaluated the effects of higher-load (HL) versus (lower-load) higher-volume (HV) resistance training on skeletal muscle hypertrophy, strength, and muscle-level molecular adaptations. Trained men (n = 15, age: 23 ± 3 years; training experience: 7 ± 3 years) performed unilateral lower-body training for 6 weeks (3× weekly), where single legs were randomly assigned to HV and HL paradigms. Vastus lateralis (VL) biopsies were obtained prior to study initiation (PRE) as well as 3 days (POST) and 10 days following the last training bout (POSTPR). Body composition and strength tests were performed at each testing session, and biochemical assays were performed on muscle tissue after study completion. Two-way within-subject repeated measures ANOVAs were performed on most dependent variables, and tracer data were compared using dependent samples t-tests. A significant interaction existed for VL muscle cross-sectional area (assessed via magnetic resonance imaging; interaction p = 0.046), where HV increased this metric from PRE to POST (+3.2%, p = 0.018) whereas HL training did not (-0.1%, p = 0.475). Additionally, HL increased leg extensor strength more so than HV training (interaction p = 0.032; HV < HL at POST and POSTPR, p < 0.025 for each). Six-week integrated non-myofibrillar protein synthesis (iNon-MyoPS) rates were also higher in the HV versus HL condition, while no difference between conditions existed for iMyoPS rates. No interactions existed for other strength, VL morphology variables, or the relative abundances of major muscle proteins. Compared to HL training, 6 weeks of HV training in previously trained men optimizes VL hypertrophy in lieu of enhanced iNon-MyoPS rates, and this warrants future research.
ABSTRACT
This study assesses if a lower dose of whey protein can provide similar benefits to those shown in previous work supplementing Army Initial Entry Training (IET) Soldiers with two servings of whey protein (WP) per day. Eighty-one soldiers consumed one WP or a calorie matched carbohydrate (CHO) serving/day during IET (WP: n = 39, height = 173 ± 8 cm, body mass = 76.8 ± 12.8 kg, age = 21 ± 3 years; CHO: n = 42, 175 ± 8 cm, 77.8 ± 15.3 kg, 23 ± 4 years). Physical performance (push-ups, sit-ups, and a two-mile run) was assessed during weeks two and eight. All other measures (dietary intake, body composition, blood biomarkers) at weeks one and nine. There was a significant group difference for fat mass (p = 0.044) as WP lost 2.1 ± 2.9 kg and had a moderate effect size (Cohen's d: -0.24), whereas the CHO group lost 0.9 ± 2.5 kg and had only a small effect size (d: -0.1). There was no significant group-by-time interaction on fat-free mass (p = 0.069). WP gained 1.2 ± 2.4 (d: 0.1) and CHO gained 0.1 ± 3 (d: 0) kg of FFM on average. There was a significant group by week 1-fat free mass interaction (p = 0.003) indicating individuals with higher initial fat-free mass benefitted more from WP. There were no group differences for push-up (p = 0.514), sit-up (p = 0.429) or run (p = 0.313) performance. For all biomarkers there was a significant effect of time as testosterone (p < 0.01), testosterone to cortisol ratio (p = 0.39), and IGF-1 (p < 0.01) increased across training and cortisol (p = 0.04) and IL-6 (p < 0.01) decreased. There were no differences in groups across IET for any of the biomarkers. We conclude one WP serving is beneficial for FM and for FFM in soldiers with high baseline FFM but may not significantly alter biomarker response or physical performance of IET soldiers who have high relative dietary protein intakes.
ABSTRACT
Decades of work have elucidated cytokine signalling and transcriptional pathways that control T cell differentiation and have led the way to targeted biologic therapies that are effective in a range of autoimmune, allergic and inflammatory diseases. Recent evidence indicates that obesity and metabolic disease can also influence the immune system1-7, although the mechanisms and effects on immunotherapy outcomes remain largely unknown. Here, using two models of atopic dermatitis, we show that lean and obese mice mount markedly different immune responses. Obesity converted the classical type 2 T helper (TH2)-predominant disease associated with atopic dermatitis to a more severe disease with prominent TH17 inflammation. We also observed divergent responses to biologic therapies targeting TH2 cytokines, which robustly protected lean mice but exacerbated disease in obese mice. Single-cell RNA sequencing coupled with genome-wide binding analyses revealed decreased activity of nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ) in TH2 cells from obese mice relative to lean mice. Conditional ablation of PPARγ in T cells revealed that PPARγ is required to focus the in vivo TH response towards a TH2-predominant state and prevent aberrant non-TH2 inflammation. Treatment of obese mice with a small-molecule PPARγ agonist limited development of TH17 pathology and unlocked therapeutic responsiveness to targeted anti-TH2 biologic therapies. These studies reveal the effects of obesity on immunological disease and suggest a precision medicine approach to target the immune dysregulation caused by obesity.